Mitochondrially Transcribed dsRNA Mediates Manganese-induced Neuroinflammation.

ABSTRACT: Manganese (Mn) is an essential trace element required for various biological functions, but excessive Mn levels are neurotoxic and lead to significant health concerns. The mechanisms underlying Mn-induced neurotoxicity remain poorly understood. Neuropathological studies of affected brain regions reveal astrogliosis, and neuronal loss, along with evidence of neuroinflammation. Here, we present a novel Mn-dependent mechanism linking mitochondrial dysfunction to neuroinflammation. We found that Mn disrupts mitochondrial transcriptome processing, resulting in the accumulation of complementary RNAs that form double-stranded RNA (dsRNA). This dsRNA is released to the cytoplasm, where it activates cytosolic sensor pathways, triggering type I interferon responses and inflammatory cytokine producti

SUBMITTER: Gokhale A 

PROVIDER: S-EPMC11870567 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature